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Consistent blind protein structure generation from NMR chemical shift data

Identifieur interne : 000E41 ( Main/Exploration ); précédent : 000E40; suivant : 000E42

Consistent blind protein structure generation from NMR chemical shift data

Auteurs : Yang Shen [États-Unis] ; Oliver Lange [États-Unis] ; Frank Delaglio [États-Unis] ; Paolo Rossi [États-Unis] ; James M. Aramini [États-Unis] ; Gaohua Liu [États-Unis] ; Alexander Eletsky [États-Unis] ; Yibing Wu [États-Unis] ; Kiran K. Singarapu [États-Unis] ; Alexander Lemak [Canada] ; Alexandr Ignatchenko [Canada] ; Cheryl H. Arrowsmith [Canada] ; Thomas Szyperski [États-Unis] ; Gaetano T. Montelione [États-Unis] ; David Baker [États-Unis] ; Ad Bax [États-Unis]

Source :

RBID : PMC:2290745

Abstract

Protein NMR chemical shifts are highly sensitive to local structure. A robust protocol is described that exploits this relation for de novo protein structure generation, using as input experimental parameters the 13Cα, 13Cβ, 13C′, 15N, 1Hα and 1HN NMR chemical shifts. These shifts are generally available at the early stage of the traditional NMR structure determination process, before the collection and analysis of structural restraints. The chemical shift based structure determination protocol uses an empirically optimized procedure to select protein fragments from the Protein Data Bank, in conjunction with the standard ROSETTA Monte Carlo assembly and relaxation methods. Evaluation of 16 proteins, varying in size from 56 to 129 residues, yielded full-atom models that have 0.7–1.8 Å root mean square deviations for the backbone atoms relative to the experimentally determined x-ray or NMR structures. The strategy also has been successfully applied in a blind manner to nine protein targets with molecular masses up to 15.4 kDa, whose conventional NMR structure determination was conducted in parallel by the Northeast Structural Genomics Consortium. This protocol potentially provides a new direction for high-throughput NMR structure determination.


Url:
DOI: 10.1073/pnas.0800256105
PubMed: 18326625
PubMed Central: 2290745


Affiliations:


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<affiliation wicri:level="2">
<nlm:aff id="aff2">Department of Biochemistry and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Department of Biochemistry and Howard Hughes Medical Institute, University of Washington, Seattle</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Bax, Ad" sort="Bax, Ad" uniqKey="Bax A" first="Ad" last="Bax">Ad Bax</name>
<affiliation wicri:level="2">
<nlm:aff id="aff1">*Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Maryland</region>
</placeName>
<wicri:cityArea>*Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda</wicri:cityArea>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Proceedings of the National Academy of Sciences of the United States of America</title>
<idno type="ISSN">0027-8424</idno>
<idno type="eISSN">1091-6490</idno>
<imprint>
<date when="2008">2008</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>Protein NMR chemical shifts are highly sensitive to local structure. A robust protocol is described that exploits this relation for
<italic>de novo</italic>
protein structure generation, using as input experimental parameters the
<sup>13</sup>
C
<sup>α</sup>
,
<sup>13</sup>
C
<sup>β</sup>
,
<sup>13</sup>
C′,
<sup>15</sup>
N,
<sup>1</sup>
H
<sup>α</sup>
and
<sup>1</sup>
H
<sup>N</sup>
NMR chemical shifts. These shifts are generally available at the early stage of the traditional NMR structure determination process, before the collection and analysis of structural restraints. The chemical shift based structure determination protocol uses an empirically optimized procedure to select protein fragments from the Protein Data Bank, in conjunction with the standard ROSETTA Monte Carlo assembly and relaxation methods. Evaluation of 16 proteins, varying in size from 56 to 129 residues, yielded full-atom models that have 0.7–1.8 Å root mean square deviations for the backbone atoms relative to the experimentally determined x-ray or NMR structures. The strategy also has been successfully applied in a blind manner to nine protein targets with molecular masses up to 15.4 kDa, whose conventional NMR structure determination was conducted in parallel by the Northeast Structural Genomics Consortium. This protocol potentially provides a new direction for high-throughput NMR structure determination.</p>
</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Canada</li>
<li>États-Unis</li>
</country>
<region>
<li>Maryland</li>
<li>New Jersey</li>
<li>Ontario</li>
<li>Washington (État)</li>
<li>État de New York</li>
</region>
<settlement>
<li>Toronto</li>
</settlement>
<orgName>
<li>Université de Toronto</li>
</orgName>
</list>
<tree>
<country name="États-Unis">
<region name="Maryland">
<name sortKey="Shen, Yang" sort="Shen, Yang" uniqKey="Shen Y" first="Yang" last="Shen">Yang Shen</name>
</region>
<name sortKey="Aramini, James M" sort="Aramini, James M" uniqKey="Aramini J" first="James M." last="Aramini">James M. Aramini</name>
<name sortKey="Baker, David" sort="Baker, David" uniqKey="Baker D" first="David" last="Baker">David Baker</name>
<name sortKey="Bax, Ad" sort="Bax, Ad" uniqKey="Bax A" first="Ad" last="Bax">Ad Bax</name>
<name sortKey="Delaglio, Frank" sort="Delaglio, Frank" uniqKey="Delaglio F" first="Frank" last="Delaglio">Frank Delaglio</name>
<name sortKey="Eletsky, Alexander" sort="Eletsky, Alexander" uniqKey="Eletsky A" first="Alexander" last="Eletsky">Alexander Eletsky</name>
<name sortKey="Lange, Oliver" sort="Lange, Oliver" uniqKey="Lange O" first="Oliver" last="Lange">Oliver Lange</name>
<name sortKey="Liu, Gaohua" sort="Liu, Gaohua" uniqKey="Liu G" first="Gaohua" last="Liu">Gaohua Liu</name>
<name sortKey="Montelione, Gaetano T" sort="Montelione, Gaetano T" uniqKey="Montelione G" first="Gaetano T." last="Montelione">Gaetano T. Montelione</name>
<name sortKey="Rossi, Paolo" sort="Rossi, Paolo" uniqKey="Rossi P" first="Paolo" last="Rossi">Paolo Rossi</name>
<name sortKey="Singarapu, Kiran K" sort="Singarapu, Kiran K" uniqKey="Singarapu K" first="Kiran K." last="Singarapu">Kiran K. Singarapu</name>
<name sortKey="Szyperski, Thomas" sort="Szyperski, Thomas" uniqKey="Szyperski T" first="Thomas" last="Szyperski">Thomas Szyperski</name>
<name sortKey="Wu, Yibing" sort="Wu, Yibing" uniqKey="Wu Y" first="Yibing" last="Wu">Yibing Wu</name>
</country>
<country name="Canada">
<region name="Ontario">
<name sortKey="Lemak, Alexander" sort="Lemak, Alexander" uniqKey="Lemak A" first="Alexander" last="Lemak">Alexander Lemak</name>
</region>
<name sortKey="Arrowsmith, Cheryl H" sort="Arrowsmith, Cheryl H" uniqKey="Arrowsmith C" first="Cheryl H." last="Arrowsmith">Cheryl H. Arrowsmith</name>
<name sortKey="Ignatchenko, Alexandr" sort="Ignatchenko, Alexandr" uniqKey="Ignatchenko A" first="Alexandr" last="Ignatchenko">Alexandr Ignatchenko</name>
</country>
</tree>
</affiliations>
</record>

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